Extract of Indigofera spicata Exerts Antiproliferative Effects on Human Colorectal and Ovarian Carcinoma Cells
Metabolic anticancer therapy based on enzymatic arginine (Arg) deprivation (ADT) is currently being evaluated in clinical trials. The combination of ADT with low doses of the plant cytotoxic analogs of Arg, canavanine (Cav) or indospicine (Isp), have been proposed as being more efficient and selective against malignant cells. The leguminous plant <i>Indigofera spicata</i> contains one of the highest known amounts of Isp. Here we demonstrate for the first time that the Isp-containing ethanolic extract from <i>I. spicata</i> is growth-inhibiting and toxic for cultured human colorectal and ovarian carcinoma cells. The extract reduces the viability of colorectal carcinoma cells two-fold under Arg-deficient conditions and entirely abrogates their residual proliferative potential (growth recovery) after the treatment. Pre-exposure of the extract to recombinant human arginase I (rhARGI) as a therapeutic Arg-depleting agent did not impact the extract's efficacy. Further development of Isp as a component of combinatorial anticancer metabolic targeting strategies is discussed.
Authors
- Dmytro Demash (ORCID: https://orcid.org/0000-0002-1378-8402)
- Mary T. Fletcher (ORCID: https://orcid.org/0000-0003-0189-3376)
- Andriy Prokopiv (ORCID: https://orcid.org/0000-0003-1690-4090)
- Nazariy T. Pokhodylo (ORCID: https://orcid.org/0000-0001-8222-5008)
- S. B. Chernyshuk (ORCID: https://orcid.org/0000-0002-9752-8084)
- Oleh Stasyk (ORCID: https://orcid.org/0000-0001-8135-6102)
- О. I. Vovk (ORCID: https://orcid.org/0000-0001-6703-457X)
- Galyna Shuvayeva (ORCID: https://orcid.org/0000-0001-7803-3900)
- M. Tupychak (ORCID: https://orcid.org/0000-0002-9880-0983)
- Yaroslav Bobak (ORCID: https://orcid.org/0000-0003-3399-1392)
- Leoni A. Kunz‐Schughart (ORCID: https://orcid.org/0000-0003-3912-6594)
Institutions
- National Academy of Sciences of Ukraine (UA)
- Lviv University (UA)
- Danylo Halytsky Lviv National Medical University (UA)
- Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv (UA)
- Helmholtz-Zentrum Dresden-Rossendorf (DE)
- National Center for Tumor Diseases (DE)
- Institute of Cell Biology (UA)
- ARC Centre of Excellence for Plant Success in Nature and Agriculture (AU)
- University Hospital Carl Gustav Carus (DE)
Publication Details
- Journal
- Toxins
- Published
- 2025-08-29
- DOI
- https://doi.org/10.3390/toxins17090431
- Citations
- 1
- Primary Topic
- Cancer Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.23